Synthesis of α- and β-lapachone derivatives from hetero diels-alder trapping of alkyl and aryl o-quinone methides

ARTICLE

Synthesis of α- and β-lapachone derivatives from hetero diels-alder trapping of alkyl and aryl o-quinone methides

Fernando de C. da Silva^I,II; Sabrina B. Ferreira^I,II; Carlos R. Kaiser^II Angelo C. Pinto^II; Vitor F. Ferreira^I,*

^IDepartamento de Química Orgânica, Instituto de Química CEG, Universidade Federal Fluminense, Campus do Valonguinho, 24020-150 Niterói-RJ, Brazil

^IIInstituto de Química, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, Cidade Universitária, 21949-900 Rio de Janeiro-RJ, Brazil

ABSTRACT

Methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes, undergo facile hetero Diels-Alder reaction with some substituted styrenes (as dienophiles) in aqueous ethanol media providing derivatives of α- and β-lapachone.

Keywords:o-Quinone methides, Knoevenagel condensation, Hetero Diels-Alder, Lapachones

RESUMO

Foram sintetizados, em um único pote reacional, alguns derivados da α- e β-lapachonas a partir de reação de hetero Diels-Alder, em etanol aquoso, entre estirenos substituídos (como dienófilos) e o-quinonas metídeos (o-QMs) metilênicas e arílicas geradas por condensação de Knoevenagel da 2-hidróxi-1,4-naftoquinona com formaldeído e aldeídos aromáticos.

Introduction

Quinones have been extensively studied for antitumoral,¹ molluscicidal,² parasiticidal,³ leishmanicidal,⁴ anti-inflammatory,⁵ fungicidal,⁶ antimicrobial⁷ and trypanocidal⁸ activities. Reports point out that the biological profiles of these molecules are centralized on their ortho or para-quinonoid moiety that generally accepts one and/or two electrons (redox cycling) to form the corresponding radical anion or dianion species in situ.⁹ Thus, the semi-quinone radicals accelerate intracellular hypoxic conditions by producing superoxide anion.^10,11 Due to this mechanism, quinones may present cytotoxicity to mammalian cells, possibly by affecting enzymes such as topoisomerases, a group of enzymes that are critical for DNA replication in cells.¹²

The data described in the literature so far clearly show that the naphthoquinone frameworks have important significance for the development of new substances with promising biological activities.^13,14 Therefore, new synthetic methodologies that could lead to the preparation of these compounds are very important.¹⁵

o-Quinone methides (o-QMs) are useful reactive intermediates in organic synthesis (Scheme 1)¹⁶ and involved in a large number of chemical reactions and biological processes, such as enzyme inhibition, reaction with phosphodiester, DNA alkylation and cross-linking.¹⁷ Since o-QMs are usually unstable intermediates, they must be generated in situ by processes that can involve photolysis of o-, m- and p-hydroxybenzyl alcohols¹⁸, thermal reactions^19,20, and anionic triggering reactions.²¹ However, some o-QMs may be sufficiently stable and can be isolated, depending on their structural arrangement.²²

Dalgliesh was the first one to suggest that an o-QM was a possible intermediate in an organic reaction.²³ However, the first example of generation and use of an o-QM in intramolecular hetero Diels-Alder reaction was reported by Brougidou and Christol.^24,25 Following this discovery many studies demonstrated that these hetero-diene moieties are suitable for [4 + 2] cycloadditions with a wide range of dienophiles.

Our group became interested in the chemistry of these intermediates in 1982²⁶ when we reported a novel preparation of the tetracyclic a- and b-pyranonaphthoquinones (3 and 4) in 70% yield by the reaction of citronellal (2)²⁷ with lawsone (1). The o-QM intermediate was generated in situ, (Scheme 1, Eq. 1) by a Knoevenagel reaction that upon hetero-Diels-Alder cycloaddition formed the pyranonaphthoquinones 3 and 4.

Recently, Nair et al. reported in a series of papers the study of the reactivity and use of several o-QMs^28,29 in intermolecular reaction Diels-Alder reaction. This three-component reaction (Scheme, Eq. 2) overcame the limitation regarding the use of aldehydes having the dienophiles in the same structure and it was used for the synthesis of several derivatives of α- and β-lapachone and other heterocyclic compounds. Both intra- and intermolecular hetero Diels-Alder reactions shown in Scheme 1 result in the 1,4-naphthoquinone as the major isomer. This methodology still attracts research groups interested in the synthesis of naphthoquinone derivatives.^30,

Despite its scope, this three-components reaction described in Eq.2 (Scheme 1) it still limited to the use of formaldehyde. Other aromatic aldehydes do not react under these conditions and most of them produce xanthenes (e.g 7, in Scheme 1) instead of Diels-Alder adducts.

In this communication we report our finds on the preparation of α- and β-lapachone derivatives via methylene and aryl o-quinone methides (o-QMs) generated in situ by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone (1) with formaldehyde and arylaldehydes (8) followed by hetero Diels-Alder reaction with substituted styrenes (9) in aqueous ethanol media (Scheme 2).

Results and Discussion

The reaction of lawsone (1), formaldehyde (8a) and substituted styrenes (9) in dioxane worked as expected according to the protocol developed by Nair et al.²⁸ (entries 1-3, Table 1). Despite the good performance achieved in previous reactions, it did not work with aromatic aldehydes even for periods exceeding 48 h of reflux (entries 4-6, Table 1).

Aiming to improve the scope of this reaction, and thus obtain various derivatives of lapachones, we decided to investigate the effect of the solvent, having in mind that the Diels-Alder reactions are accelerated by acids. Several reaction conditions were investigated, however best results were achieved by the reaction in ethanol/water in the proportion of 1:1 under reflux. The results are summarized in Table 2.

Comparing the results described in Table 1 (entries 1-3) with those of Table 2 (entries 1-3), we can observe that the mixture of solvents ethanol/water had effect on the yields, reaction time and the ratio between isomers α and β. The reactions were faster and the yields improved as well the proportion of β isomer.

The effect of ethanol/water solvent mixture was more significant in the reactions with aromatic aldehydes (8b-d). The reactions that had not worked previously, in this new condition produced the disubstituted naphthoquinones a (syn:anti, 10d-f) and β (syn:anti, 11d-f) in good yields (entries 3-6, Table 2). A very important point that should be emphasized was the high proportion of β-isomer (11d-f) under these new conditions.

Each of these reactions produced a mixture of α and β isomers that were composed of syn and anti diastereoisomers. In most cases the proportion of the anti isomer was higher than the syn (10d-f). The four compounds of these mixtures were separated by flash column chromatography and their structures were determined by 1D and 2D NMR techniques and by ESI-TOF mass spectrometry. The α and β-isomers (10d-f and 11d-f) could be distinguished by the hydrogens of the aromatic region because of a more symmetrical pattern of the α- isomers in comparison with that of the β isomer. The diastereoisomers syn and anti were distinguished by the coupling constants of hydrogens H-3 and H-4 of the pyran rings that showed J equal to 2.4/5.9 and 11.0/7.1 Hz (J_3a,4/J_3b,4) for the syn and anti isomers, respectively and hydrogens H-3 and H-2 with coupling constants values of 2.4/12.0 Hz (J_3a,2/J_3b,2) for syn isomers and 2.2 and 11.2 Hz (J_3a,2/J_3b,2) for anti isomers.³²

Recently, Peng and co-workers³³ performed DFT calculations for the reaction between unsubstituted o-QM and several dienophiles, including styrene. The proposed molecular mechanisms for these reactions were postulated to be asynchronicity concert cycloaddition mechanism. The activation energies for the ortho attack modes is lower than meta ones. Their calculations also show that the effect of solvent decreases the activation energy and increases the asynchronicity. Regarding the regioselectivity, our reactions are in complete agreement with a [4+2] cycloaddition of the o-QM with the styrene in asynchronous fashion by zwitterion-like transition state. Xu and co-workers³⁰ generated in situ the o-QMs I and II (Scheme 2) and reacted then with several silyl enol ethers obtaining regioselectively α-lapachone derivatives with anti stereoselectivity in moderate to high yield. The regioselectivity was rationalized by considering favorable pathway to a zwitterion-like transition state of lower energy between the reactants. DFT calculation indicated that o-QM I has lower LUMO energy than II. However, no rationalization was attempted by the author to explain the anti stereoselectivity.

Since the intermediate I is the most stable one, we can speculated that it forms preferentially the α- and β-anti adducts with the proper regiochemistry by a chair-like endo transition state as indicated in Figure 1.

The acceleration of the Diels-Alder reactions by aqueous media is well known.³⁴ However, the acidity of the mixture ethanol:water is more relevant for success of the reactions. In an attempt to investigate this hypothesis, we decided to carry out the reactions of the compound 1 with aldehydes and styrenes in dioxane, containing catalytic amount of acetic acid (entries 7 and 8, Table 2). The comparison between the experiments of entries 1 and 7 of Table 2 clearly show the effect of the acidic media and increasing the proportion of β-isomers. In these experiments formation of the by-product benzoxanthene (type 7) was negligible.

Conclusions

In summary, the methodology described by Nair et al. has been improved, resulting in β-pyranonaphthoquinones more selectively and in better yields and lower reaction time. Additionally, with this methodology it was possible to use any type of aldehyde, and not only formaldehyde.

Acknowledgments

This work was supported by CNPq (National Council of Research of Brazil), CAPES, FINEP, PRONEX-FAPERJ (E-26/171.512.2006), UFRJ and UFF.

Supplementary Information

Supplementary data are available free of charge at http://jbcs.org.br, as PDF file.

References

1. Lee, J. H.; Cheong, J. H.; Park, Y. M.; Choi, Y. H.; Pharmacolog. Res. 2005, 51, 553; Skibo, E. B.; Xing, C.; Dorr, R. T.; J. Med. Chem. 2001, 44, 3545.

2. dos Santos, A. F.; Ferraz, P. A. L.; de Abreu, F. C.; Chiari, E.; Goulart, M. O. F.; Sant'Ana, A. E. G.; Planta Med. 2001, 67, 92; Barbosa, T. P.; Camara, C. A.; Silva, T. M. S.; Martins, R. M.; Pinto, A. C.; Vargas, M. D.; Bioorg. Med. Chem. 2005, 13, 6464.

3. Ferreira, V. F.; Jorqueira, A.; Souza, A. M. T.; Da Silva, M. N.; de Souza, M. C. B. V.; Gouvêa, R. M.; Rodrigues, C. R.; Pinto, A. V.; Castro, H. C.; Santos, D. O.; Araújo, H. P.; Bourguignon, S. C.; Bioorg. Med. Chem. 2006, 14, 5459; Jorqueira, A.; Gouvêa, R. M.; Ferreira, V. F.; da Silva, M. N.; de Souza, M. C. B. V.; Zuma, A. A.; Cavalcanti, D. F. B.; Araújo, H. P.; Bourguignon, S. C.; Parasitol. Res. 2006, 99, 429; Silva-Jr, E. N.; Menna-Barreto, R. F. S.; Pinto, M. C. F. R.; Silva, R. S. F.; Teixeira, D. V.; de Souza, M. C. B. V.; Simone, C. A.; de Castro, S. L.; Ferreira, V. F.; Pinto, A. V.; Eur. J. Med. Chem. 2008, 43, 1774.

4. Teixeira, M. J.; de Almeida, Y. M.; Viana, J. R.; Holanda, J. G.; Rodrigues, T. P.; Prata, J. R. C..; Coelho, I. V. B.; Rao, V. S.; Pompeu, M. M. L.; Phytother. Res. 2001, 15, 44.

5. de Almeida, E. R.; Filho, A. A. S.; dos Santos E. R.; Lopes C. A. C.; J. Ethnopharmacol. 1990, 29, 239.

6. Gafner, S.; Wolfender, J. L.; Nianga, M.; Stoeckli-Evans, H.; Hostettmann, K.; Phytochemistry 1996, 42, 1315.

7. Tabata, M.; Tsukada, M.; Fukui, H.; Planta Med. 1982, 44, 234.

8. Salas, C.; Tapia, R. A.; Ciudad, K.; Armstrong, V.; Orellana, M.; Kemmerling, U.; Ferreira, J.; Maya, J. D.; Morello, A.; Bioorg. Med. Chem. 2008, 16, 668; Dubin, M.; Villamil, S. H. F.; Stoppani, A. O. M.; Medicina-Buenos Aires 2001, 61, 343; Pinto, C. N.; Dantas, A. P.; de Moura, K. C. G.; Emery, F. S.; Polequevitch, P. F.; Pinto, M. D.; de-Castro, S. L.; Pinto, A. V.; Arzneim. Forsch. 2000, 50, 1120.

9. Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.; Debreu, M.-A.; Landry, V.; Sergheraert, C.; Croft, S. L.; Krauth-Siegel, R. L.; Davioud-Charvet, E.; J. Med. Chem. 2001, 44, 548.

10. Santos, E. V. M.; Carneiro, J. W. M.; Ferreira, V. F.; Bioorg. Med. Chem. 2004, 12, 87.

11. Hickman, J. A.; Curr. Opin. Genet. Dev. 2002, 12, 67.

12. Esteves-Souza, A.; Figueiredo, D. V.; Esteves, A.; Camara, C. A.; Vargas, M. D.; Pinto, A. C.; Echevarria, A.; Braz. J. Med. Biol. Res. 2007, 40, 1399.

13. Monks, T. J., Jones, D. C.; Curr. Drug Metabolism 2002, 3, 425.

14. Silva, M. N.; Ferreira, V. F.; de Souza, M. C. B. V.; Quim. Nova 2003, 26, 407.

15. da Silva A. R.; da Silva, A. M.; Ferreira, A. B. B.; Bernardes, B. O.; da Costa, R. L.; J. Braz. Chem. Soc. 2008, 19, 1230; Silva, R. S. E.; de Amorim, M. B.; Pinto, M. D. C. F. R.; Emery, F. S.; Goulart, M. O. F.; Pinto, A. V.; J. Braz. Chem. Soc. 2007, 18, 759; Uliana, M. P.; Vieira, Y. W.; Donatoni, M. C.; Corrêa, A. G.; Brocksom, U.; Brocksom, T. J.; J. Braz. Chem. Soc. 2008, 19, 1484; Vieira, Y. W.; Nakamura, J.; Finelli, F. G.; Brocksom, U.; Brocksom, T. J.; J. Braz. Chem. Soc. 2007, 18, 448.

16. Van De Walters, R. W.; Pettus, T. R. R.; Tetrahedron 2002, 58, 5367.

17. Wang, P.; Song, Y.; Zhang, L. X.; He, H. P.; Zhou, X.; Curr. Med. Chem. 2005, 12, 2893.

18. Brousmiche, D. W.; Wan, P.; J. Photochem. Photobiol., A 2002, 149, 71.

19. Dorrestijn, E.; Pugin, R.; Nogales, M. V. C.; Mulder, P.; J. Org. Chem. 1997, 62, 4804.

20. Wojciechowski, K.; Dolatowska, K.; Tetrahedron 2005, 61, 8419.

21. van de Water, R. W.; Magdziak D. J.; Chau J. N.; Pettus, T. R. R.; J. Am. Chem. Soc. 2000, 122, 6502; Jones, R. M.; van de Water, R. W.; Lindsey, C. C.; Hoarau, C.; Ung, T.; Pettus, T. R. R.; J. Org. Chem. 2001, 66, 3435; Kiselyov, A. S.; Tetrahedron Lett. 2001, 42, 3053.

22. da Silva, M. N.; Ferreira, S. B.; Jorqueira, A.; de Souza, M. C. B. V.; Pinto, A. V.; Kaiser, C. R.; Ferreira, V. F.; Tetrahedron Lett. 2007, 48, 6171.

23. Dalgliesh, C. E.; J. Am. Chem. Soc. 1949, 71, 1697.

24. Brougidou, J.; Christol, H.; C. R. Hebd. Acad. Sci. 1963, 257, 3149.

25. Brougidou, J., Christol, H.; C. R. Hebd. Acad. Sci. 1963, 257, 3323.

26. Ferreira, V. F.; Coutada, L. C.; Pinto M. C. F. R.; Pinto, A. V.; Synth. Commun. 1982, 12, 195.

27. Ferreira, V. F.; Pinto, A. V.; Coutada, L. C. M.; An. Acad. Brasil. Cienc. 1980, 52, 477.

28. Nair, V.; Mathew, B.; Rath, N. P.; Vairamani, M; Prabhakar, S.; Tetrahedron 2001, 57, 8349.

29. Nair, V.; Jayan, C. N.; Radhakrishnan, K. V.; Anilkumar, G.; Rath, N. P.; Tetrahedron 2001, 57, 5807; Nair, V.; Treesa, P. M.; Tetrahedron Lett. 2001, 42, 4549; Nair, V.; Treesa, P. M.; Jayan, C. N.; Rath, N. P.; Vairamani, M.; Prabhakar, S.; Tetrahedron 2001, 57, 7711; Nair, V.; Menon, R. S.; Vinod, A. U.; Viji, S.; Tetrahedron Lett. 2002, 43, 2293.

30. Peng, D. -Q.; Liu, Y.; Lu, Z. -F.; Shen, Y. -M.; Xu, J. -H.; Synthesis 2008, 1182.

31. Teimouri, M. B.; Khavasi, H. R.; Tetrahedron 2007, 63, 10269.

32. General Procedure for preparing 10a-f and 11a-f. To a round-bottom flask equipped with a magnetic stirring bar was added dissolved lawsone (1 mmol) with water (10 mL) and ethanol (10 mL). Then, the appropriate aldehyde (8 mmols for paraformaldehyde or 3 mmols for arylaldehydes) was added, followed by dropwise addition of the substituted styrenes (3 mmol). The reaction mixture was stirred under reflux until consumption of the starting material (5-8 h). The ethanol was removed under reduced pressure and ethyl acetate (50 mL) was added to the residue and the mixture was washed with saturated aqueous solution of sodium bicarbonate (2 × 20 mL). The organic phase was washed with water (2 × 50 mL), dried over anhydrous sodium sulphate, filtered and concentrated under vacuum. The residual crude product was purified by column chromatography on silica gel using gradient mixture of hexane-ethyl acetate.

33. Wang, H.; Wang, Y.; Han, K. -L.; Peng, X. -J.; J. Org. Chem. 2005, 70, 4910.

34. Wijnen, J. W.; Engberts, J. B. F. N.; J. Org. Chem. 1997, 62, 2039; Deshpande, S. S.; Kumar, A.; Tetrahedron, 2005, 61, 8025; Sarma, D.; Pawar, S. S; Deshpande, S. S.; Kumar, A. Tetrahedron Lett. 2006, 47, 3957.

35. Chen, Y.; Wu, S.; Tu, S.; Li, C.; Shi, F.; J. Heterocycl. Chem. 2008, 45, 931.

Received: January 6, 2009

Web Release Date: August 24, 2009

Supplementary Information

EXPERIMENTAL

General information

Melting points were observed on a Fischer Jones and are uncorrected. Analytical grade solvents were used. Dioxane was distilled before being used. Reagents were purchased from Aldrich or Acros Chemical Co. Column chromatography was performed on silica gel 60 (Merck 70-230 mesh). Yields refer to chromatographically and spectroscopically homogeneous materials. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm E. Merck silica gel plates (60F-254) using UV light as visualizing agent and either an ethanolic solution of sulfate. Infrared spectra were recorded on a Perkin-Elmer FT-IR Spectrum One spectrophotometer, calibrated relative to the 1601.8 cm^-1 absorbance of polystyrene. NMR spectra were recorded on a Varian Unity Plus VXR (300 MHz) equipament in DMSO-d₆ and CDCl₃ solutions and tetramethylsilane was used as the internal standard (δ = 0 ppm). High resolution mass spectra (HRMS) were recorded on an MICROMASS Q-TOF MICRO Mass spectrometer using ESI-TOF (electrospray ionization-time of flight).

General Procedure for preparation of 10a-f and 11a-f in dioxane media

To a round-bottom flask equipped with a magnetic stirring bar was added lawsone (1 mmol), appropriate aldehyde (8 mmols for paraformaldehyde or 3 mmols for arylaldehydes) and dissolved with dioxane (20 mL). Then substituted styrene (3 mmols) was added dropwise and reaction mixture was stirred under reflux until consumption of the starting material. The dioxane was evaporated, ethyl acetate was added and mixture was washed with saturated aqueous solution of sodium bicarbonate. The organic layer was washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residual crude product was purified via silica-gel chromatography, using gradient mixture of hexane-ethyl acetate.

General Procedure for preparation of 10a-f and 11a-f in aqueous ethanol media

To a round-bottom flask equipped with a magnetic stirring bar lawsone was dissolved (1 mmol) with water (10 mL) and ethanol (10 mL). Then, the appropriate aldehyde (8 mmols for paraformaldehyde or 3 mmols for arylaldehydes) was added. Styrenes substituted (3 mmols) was added drop-wise and reaction mixture was stirred under reflux until consumption of the starting material. The ethanol was removed under reduced pressure, ethyl acetate was added in the residue and mixture was washed with saturated aqueous solution of sodium bicarbonate. The combined organic extracts washed with water, and dried over anhydrous sodium sulphate, was filtered and concentrated under pressure reduced. The residual crude product was purified via silica-gel chromatography, using gradient mixture of hexane-ethyl acetate.

General Procedure for preparation of 10a/d and 11a/d in dioxane/acetic acid media

The general procedure was like the general procedure reported for dioxane media with additional of some drops of acetic acid.

2-phenyl-3,4-dihydro-2H-benzo[g]chromene-5, 10-dione (10a)

Yellow solid, m.p.= 168-170 ºC; IR (KBr, cm^-1): ν 1679, 1649, 1617, 1260, 1202, 1063, 958, 910, 721; ¹H NMR (CDCl₃, 300 MHz): d 2.15 (1H, dddd, J = 2.6, 3.2, 5.7 and 14.0 Hz, H-3a), 2.30 (1H, dddd, J = 2.2, 6.2, 6.5 and 14.0 Hz, H-3b), 2.63 (1H, ddd, J = 3.2, 6.2 and 13.7 Hz, H-4a), 2.77 (1H, ddd, J = 2.2, 5.7, and 13.7 Hz, H-4b), 5.22 (1H, dd, J = 2,6 e 6,5 Hz, H-2), 7.32 - 7.40 (5H, m, 2-phenyl), 7.68 (2H, dddd, J = 2.0, 7.5, 9.2 and 11.0 Hz, H-8 e H-7), 8.10 (2H, dddd, J =2.0, 7.5, 9.2 and 10.9 Hz, H-9 e H-6); ¹³C NMR (CDCl₃, 75 MHz): d 18.3 (C-4), 27.6 (C-3), 78.8 (C-2), 121.4 (C-4a), 125.6 (C-4'-phenyl), 125.8 (C-6), 126.1 (C-9), 128.1 (C-2'-phenyl), 128.4 (C-3'-phenyl), 130.8 (C-9a), 131.7 (C-5a), 132.9 (C-7, C-8), 133.7 (C-Har), 139.1 (C-1'), 152.2 (C-10a), 184.0 (C-5 and C-10). HRMS (ESI) calcd for C₁₉H₁₄O₃: 290.0943, Found: 290.0336.

2-(p-tolyl)-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10b )

Yellow solid, m.p.= 135-137ºC; IR (KBr, cm^-1): ν 1677, 1645, 1617, 1595, 1341, 1300, 1258, 1200, 1065, 958, 910, 816, 720; ¹H NMR (CDCl₃, 300 MHz): d 2.06 (1H, dddd, J = 2.6, 3.4, 6.0 and 13.0 Hz, H-3a), 2.31 (1H, dddd, J = 2.3, 6.4, 6.3 and 13.0 Hz, H-3b), 2.36 (1H, s, CH₃), 2,64 (1H, ddd, J = 3.4, 6.4 and 12.7 Hz, H-4a), 2.75 (1H, ddd, J = 2.3, 6.0, and 12.7 Hz, H-4b), 5.18 (1H, dd, J = 2.6 and 6.3 Hz, H-2), 7.1 (2H, dd, J = 7.7 Hz, H-meta tolyl), 7.27 (2H, dd, J = 7.7 Hz, H-orto tolyl), 7.69 (2H, dddd, J = 1.0, 7.3, 9.0 and 10.7 Hz, H-8 e H-7), 8.09 (2H, dddd, J = 1.0, 7.3, 9.0 and 10.7 Hz, H-9 e H-6); ¹³C NMR (CDCl₃, 75 MHz): δ 18.8 (C-4), 21.4 (CH₃), 28.0 (C-3), 79.2 (C-2), 121.8 (C-4a), 126.1 (C-6), 126.2 (C-9), 126.5 (C-2'), 129.5 (C-3'), 131.3 (C-9a),133.7 (C-4'), 134.1 (C-1'), 136.3 (C-5a), 138.3 (C-1'), 155.8 (C-10a), 179.6 and 184.0 (C-5 and C-10). HRMS (ESI) calcd for C₂₀H₁₆O₃: 304.1099, Found: 304.1261.

2-(2,4-dimethylphenyl)-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10c )

Yellow solid, m.p.= 148-152 ⁰C; IR (KBr, cm^-1): ν 1673, 1646, 1617, 1590, 1261,1204, 1299, 1063, 961, 825, 718, 676; ¹H NMR (CDCl₃, 300 MHz): d 1.99 (1H, dddd, J = 2.4, 3.4, 5.9 and 13.2 Hz, H-3a), 2,25 (1H, dddd, J = 2.4, 6.4, 7.8 and 13.2 Hz, H-3b), 2.32 (3H, s, CH₃), 2.34 (3H, s, CH₃), 2.64 (1H, ddd, J = 3.4, 6.4 and 13.0 Hz, H-4a), 2.85 (1H, m, ddd, J = 2.4, 5.9, and 13.0 Hz, H-4b), 5.25 (1H, dd, J = 2.4 and 7.8 Hz, H-2), 7.01 (1H, s, H-meta tolyl), 7.06 (1H, d, J = 7.8 Hz, H-orto tolyl), 7.30 (1H, d, J = 7.8 Hz, H-meta tolyl), 7.69 (2H, dddd, J = 2.0, 7.8, 9.2 and 10.7 Hz, H-8 e H-7), 8.10 (2H, dddd, J = 2.0, 7.6, 9.2 and 10.9 Hz, H-9 e H-6); ¹³C NMR (CDCl₃, 75 MHz): d 19.2 (CH₃), 19.6 (C-4), 21.3 (CH₃), 27.2 (C-3), 77.0 (C-2), 121.6 (C-4a), 125.9 (C-5' orto tolyl), 126.2 and 126.5 (C-6 and C-9), 127.3 (C-6'), 131.6 (C-3' orto tolyl), 131.3 (C-9a), 132.2 (C-5a), 133.3 and 134.1 (C-7 and C-8), 134.7 and 134.9 (C-2' and C-4'), 138.1 (C-1'), 156.2 (C-10a), 179.6 and 184.0 (C-5 and C-10). HRMS (ESI) calcd for C₂₁H₁₈O₃: 318.1256, Found: 318.1876

4-(4-nitrophenyl)-2-p-tolyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10d ), Syn isomer

Yellow solid, m.p.= 205-207 ºC; IR (KBr, cm^-1): ν 1677, 1649, 1612, 1516, 1344, 1305, 1266, 1209, 1106, 968, 900, 856, 818, 725; ¹H NMR (CDCl₃, 300 MHz): d 2.25 (1H, dt, J = 2.4 and 14.3 Hz, H-3a), 2.35 (3H, s, CH₃), 2.44 (1H, ddd, J = 5.7, 11.9 and 14.3 Hz, H-3b), 4.52 (1H, dd, J = 2.4 and 5.7 Hz, H-4), 4.99 (1H, dd, J = 2.4 and 11.9 Hz, H-2), 7.17 (1H, d, J = 8.5 Hz, H-meta p-tolyl), 7.22 (1H, d, J = 8.5 Hz, H-ortho p-tolyl), 7.46 (1H, d, J = 8.6 Hz, H-ortho 4-nitrophenyl), 7.71-7.77 (1H, m, H-7), 7.71-7.77 (1H, m, H-8), 8.00-8.06 (1H, m, H-9), 8.17-8.22 (1H, m, H-6), 8.22 (1H, d, J = 8.6 Hz, H-meta 4-nitrophenyl); ¹³C NMR (CDCl₃, 75 MHz): d 21.0 (CH₃), 35.2 (C-4), 36.5 (C-3), 75.0 (C-2), 120.2 (C-4a), 124.0 (C-3' 4-nitrophenyl), 126.0 (C-9), 126.3 (C-2' 4-nitrophenyl), 126.5 (C-7), 128.5 (C-3' p-tolyl), 129.3 (C-2' p-tolyl), 131.0 (C-9a), 131.7 (C-5a), 133.3 (C-6), 134.2 (C-8), 135.0 (C-4' p-tolyl), 138.5 (C-1' p-tolyl), 146.8 (C-4' 4-nitrophenyl), 151.0 (C-1' 4-nitrophenyl), 156.6 (C-10a), 179.0 (C-10), 183.1 (C-5).

4-(4-nitrophenyl)-2-p-tolyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10d ), Anti isomer

Yellow solid, m.p.= 231-234 ºC; IR (KBr, cm^-1): ν 1677, 1650, 1607, 1511, 1345, 1301, 1266, 1258, 1199, 961, 724; ¹H NMR (CDCl₃, 300 MHz): d 2.25 (1H, dt, J = 2.4 and 14.3 Hz, H-3a), 2.35 (3H, s, CH₃), 2.62 (1H, ddd, J = 2.2, 7.1 and 14.4 Hz, H-3b), 4.40 (1H, dd, J = 7.1 and 10.7 Hz, H-4), 5.20 (1H, dd, J = 2.0 and 11.0 Hz, H-2), 7.18 (1H, d, J = 8.1 Hz, H-meta p-tolyl), 7.30 (1H, d, J = 8.1 Hz, H-ortho p-tolyl), 7.35 (1H, d, J = 8.8 Hz, H-ortho 4-nitrophenyl), 7.67-7.74 (1H, m, H-7), 7.67-7.74 (1H, m, H-8), 7.90-7.93 (1H, m, H-9), 8.11-8.17 (1H, m, H-6), 8.13 (1H, d, J = 8.8 Hz, H-meta 4-nitrophenyl); ¹³C NMR (CDCl₃, 75 MHz): d 21.0 (CH₃), 29.6 (C-3), 38.6 (C-3), 79.2 (C-2), 122.8 (C-4a), 123.9 (C-3' 4-nitrophenyl), 125.9 (C-9), 126.2 (C-2' 4-nitrophenyl), 126.4 (C-7), 127.6 (C-3' p-tolyl), 129.3 (C-2' p-tolyl), 130.8 (C-9a), 131.8 (C-5a), 133.3 (C-6), 134.2 (C-8), 134.8 (C-4' p-tolyl), 138.6 (C-1' p-tolyl), 146.4 (C-4' 4-nitrophenyl), 151.2 (C-1' 4-nitrophenyl), 157.4 (C-10a), 183.2 (C-10), 186.8 (C-5).

4-Phenyl-2-p-tolyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10e )

Yellow solid, m.p. = 203-205 ºC; IR (KBr/cm^-1): 1678, 1647, 1615, 1365, 1336, 1302, 1257, 1194, 1068, 1043, 960, 894, 812, 760, 725, 702. ¹H NMR (300 MHz, CDCl₃): d 2.13-2.32 (1H, m, H-3a), 2.34 and 2.35 (3H, s, CH₃), 2.44 (1H, ddd, J = 2.0, 7.3 and 14.4 Hz, H-3b), 4.29 (1H, dd, J = 7.3 and 11.0 Hz, H-4 anti isomer) and 4.46 (1H, dd, J = 1.5 and 5.7 Hz, H-4 syn isomer), 5.06 (1H, dd, J = 3.2 and 11.0 Hz, H-2 syn isomer) and 5.12 (1H, dd, J = 1.2 and 11.0 Hz, H-2 anti isomer), 7.14-7.34 (4H, m, p-tolyl), 7.14-7.34 (5H, m, Ph), 7.63-7.72 (1H, m, H-7), 7.63-7.72 (1H, m, H-8), 7.91-7.94 (1H, m, H-9 anti isomer) and 8.02-8.05 (1H, m, H-9 syn isomer), 8.11-8.18 (1H, m, H-6). ¹³C NMR (75 MHz, CDCl₃): d 21.4 (CH₃), 35.6 and 39.3 (C-4), 37.3 and 41.2 (C-3), 75.5 and 79.9 (C-2), 125.0 (C-4a), 126.5 and 126.6 (C-9), 126.7 (C-7), 126.8 (C-2' Ph), 127.1 (C-3' Ph), 128.0 (C-3' p-tolyl), 128.9 and 129.1 (C-4' Ph), 129.5 and 129.6 (C-2' p-tolyl), 131.2 (C-9a), 132.5 (C-5a), 133.3 and 133.4 (C-6), 134.3 and 134.4 (C-8), 135.8 (C-4' p-tolyl), 138.6 (C-1' p-tolyl), 143.9 (C-4' Ph), 157.5 (C-10a), 179.9 (C-10), 183.4 (C-5).

4-(thiophen-2-yl)-2-p-tolyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10f ), Syn isomer

Yellow solid, m.p.= 123-125 ºC; IR (KBr, cm^-1): ν 1680, 1650, 1614, 1338, 1299, 1261, 1205, 1063, 959, 896, 815, 721; ¹H NMR (CDCl₃, 300 MHz): δ 2.22-2.39 (2H, m, H-3), 2.36 (3H, s, CH₃), 4.70 (1H, ddd, J = 0.7, 1.9 and 4.9 Hz, H-4), 5.23 (1H, dd, J = 2.9 and 11.2 Hz, H-2), 6.92 (1H, dt, J = 1.0 and 3.4 Hz, H-3' thiophen-2-yl), 6.96 (1H, dd, J = 3.7 and 5.1 Hz, H-4' thiophen-2-yl), 7.20 (1H, dd, J = 1.2 and 5.1 Hz, H-5' thiophen-2-yl), 7.20 (1H, d, J = 8.0 Hz, H-meta), 7.28 (1H, d, J = 8.0 Hz, H-ortho), 7.67-7.76 (1H, m, H-7), 7.67-7.76 (1H, m, H-8), 8.06-8.09 (1H, m, H-9), 8.13-8.16 (1H, m, H-6); ¹³C NMR (CDCl₃, 75 MHz): d 21.5 (CH₃), 30.9 (C-4), 37.4 (C-3), 76.0 (C-2), 122.0 (C-4a), 124.5 (C-5' thiophen-2-yl), 125.5 (C-9), 126.5 (C-7), 126.7 (C-4' thiophen-2-yl), 127.3 (C-3' p-tolyl), 129.6 (C-2' p-tolyl), 131.4 (C-4' p-tolyl), 132.3 (C-6), 133.5 (C-8), 134.4 (C-3' thiophen-2-yl), 136.0 (C-1' p-tolyl), 138.6 (C-2' thiophen-2-yl), 147.2 (C-11), 176.5 (C-10), 183.6 (C-5).

4-(thiophen-2-yl)-2-p-tolyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione ( 10f ), Anti isomer

Yellow solid, m.p.= 172-175 ºC; IR (KBr, cm^-1): ν 1678, 1649, 1611, 1363, 1333, 1300, 1256, 1192, 1041, 954, 892, 847, 814, 721; ¹H NMR (CDCl₃, 300 MHz): δ 2.28-2.43 (1H, m, H-3a), 2.40 (3H, s, CH₃), 2.68 (1H, ddd, 2.1, 7.1 and 14.4 Hz, H-3b), 4.57 (1H, dd, J = 7.1 and 11.0 Hz) and 4.65 (1H, dd, J = 1.0 and 3.2 Hz) H-4 conformers, 5.23 (1H, dd, J = 1.9 and 11.5 Hz) and 5.35 (1H, dd, J = 4.4 and 10.0 Hz) H-2 conformers, 6.89 and 6.90 (1H, dd, J = 1.0 and 3.4 Hz, H-3' thiophen-2-yl conformers), 6.86 and 6.95 (1H, dd, J = 3.7 and 5.1 Hz, H-4' thiophen-2-y conformers), 7.06 and 7.18 (1H, dd, J = 1.2 and 5.1 Hz, H-5' thiophen-2-yl conformers), 7.24 and 7.25 (1H, d, J = 8.0 Hz, H-meta conformers), 7.30 and 7.36 (1H, d, J = 8.0 Hz, H-ortho conformers), 7.54 and 7.57 (1H, td, J = 1.2 and 7.6 Hz, H-8 conformers), 7.63 and 7.65 (1H, dt, J = 1.2 and 7.6 Hz, H-7 conformers), 7.89 (1H, d, J = 7.6 Hz, H-9), 8.09 and 8.13 (1H, dd, J = 1.5 and 7.6 Hz, H-6 conformers) ; ¹³C NMR (CDCl₃, 75 MHz): d 21.4 (CH₃), 30.9 (C-4), 41.5 (C-3), 79.9 (C-2), 124.4 (C-4a), 124.6 (C-5' thiophen-2-yl), 126.4 (C-9), 126.5 (C-7), 126.6 (C-4' thiophen-2-yl), 127.0 (C-3' p-tolyl), 129.6 (C-2' p-tolyl), 131.2 (C-4' p-tolyl), 132.5 (C-6), 133.4 (C-8), 134.4 (C-3' thiophen-2-yl), 135.5 (C-1' p-tolyl), 138.7 (C-2' thiophen-2-yl), 146.6 (C-11), 179.8 (C-10), 183.7 (C-5).

2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11a )

Orange solid, m.p.= 161-163 ⁰C; IR (KBr, cm^-1): ν 1696, 1647, 1605,1573, 1397, 1300, 1280, 1232, 1158, 1093, 922, 700; ¹H NMR (CDCl₃, 300 MHz): δ 2.08 (1H, dddd, J = 2.7, 3.2, 5.6 and 13.8 Hz, H-3a), 2.33 (1H, dddd, J = 3.4, 6.3, 7.4 and 13.8 Hz, H-3b), 2.60 (1H, ddd, J = 3.2, 6.3 and 8.8 Hz, H-4a), 2.76 (1H, ddd, J = 3.4, 5.6 and 8.8 Hz H-4b), 5.27 (1H, dd, J = 2.7 and 7.4 Hz, H-2), 7.39-7.46 (5H, m, 2-phenyl), 7.53 (1H, ddd, J = 1.2, 7.4 and 8.6 Hz,H-8), 7.64 (1H, ddd, J = 1.4, 7.6 and 9.1 Hz, H-9), 7.83 (1H, dd, J = 0.9 and 7.6 Hz, H-10), 8.01 (1H, dd, J = 1.4 and 7.6 Hz, H-7); ¹³C NMR (CDCl₃, 75 MHz): d 18.2 (C-4), 28.2 (C-3), 79.9 (C-2), 113.8 (C-4a), 123.9 (C-10), 125.6 (C-7), 125.7 (C-4'-phenyl), 128.4 (C-8), 128.5 (C-2'-phenyl), 128.6 (C-3'-phenyl), 129.8 (C-6a), 130.6 (C-9), 131.9 (C-1'-phenyl), 139.2 (C-10a), 162.7 (C-10b), 178.7 and 179.0 (C-5 and C-6). HRMS (ESI) calcd for C₁₉H₁₄O₃: 290.0943, Found: 290.0344

2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11b )

Orange solid, m.p.= 165-167 ⁰C; IR (KBr, cm^-1): ν 1697, 1647, 1605, 1590, 1572, 1393, 1301, 1280, 1158, 1076, 922,771; ¹H NMR (CDCl₃, 300 MHz): δ 2.06 (1H, dddd, J = 2.4, 3.6, 5.6 and 12.7 Hz, H-3a), 2.31 (1H, dddd, J = 3.1, 6.2, 7.8 and 12.7 Hz, H-3b), 2.40 (3H, s, CH₃), 2.59 (1H, ddd, J = 3.6, 6.2 and 8.7 Hz, H-4a), 2.77 (1H, ddd, J = 3.1, 5.6 and 8.7 Hz H-4b), 5.24 (1H, dd, J = 2.4 and 7.8 Hz, C-2), 7.25 (2H, d, J = 7.7 Hz, H-meta tolyl), 7.32 (2H, d, J = 7.7 Hz, H-orto tolyl), 7.51 (1H, ddd, J = 1.4, 7.5 and 8.7 Hz, H-8), 7.62 (1H, ddd, J = 1.4, 7.5 and 9.0 Hz, H-9), 7.81 (1H, dd, J = 1.2 and 7.8 Hz, H-10), 8.01 (1H, dd, J = 1.4 and 7.5 Hz, H-7); ¹³C NMR (CDCl₃, 75 MHz): δ 18.7 (C-4), 21.4 (CH₃), 28.6 (C-3), 80.4 (C-2), 114.3 (C-4a), 124.3 (C-10), 126.1 (C-7), 128.9 (C-8), 129.7 (C-2'-phenyl), 130.2 (C-6a), 131.0 (C-3'-phenyl), 132.4 (C-9'), 135.1 (C-1'-phenyl), 136.7 (C-4'-phenyl), 138.7 (C-10a), 163.2 (C-10b), 178.8 and 179.8 (C-5 and C-6). HRMS (ESI) calcd for C₂₀H₁₆O₃: 304.1099, Found: 304.1612

2-(2,4-dimethylphenyl)-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11c )

Orange solid, m.p.= 164-167 ⁰C; IR (KBr, cm^-1): ν 1694, 1646, 1603, 1574, 1394, 1283, 1231, 1034, 998, 775; ¹H NMR (CDCl₃, 300 MHz): δ 1.99 (1H, dddd, J = 2.4, 3.0, 5.3 and 12.2 Hz, H-3a), 2.26 (1H, dddd, J = 2.4, 6.6, 7.8 and 12.2 Hz, H-3b), 2.36 (3H, s, CH₃); 2.38 (3H, s, CH₃), 2.59 (1H, ddd, J = 3.0, 6.6 and 8.7 Hz, H-4a), 2.85 (1H, ddd, J = 2.4, 5.3 and 8.7 Hz H-4b), 5.35 (1H, dd, J = 2.4 and 7.8 Hz, H-2), 7.10 (2H, d, J = 7.8 Hz, H-orto and meta tolyl), 7.33 (1H, d, J = 7.8 Hz, H-meta tolyl), 7.51 (1H, ddd, J = 1.2, 7.5 and 8.7 Hz,H-8), 7.61 (1H, ddd, J = 1.4, 7.5 and 9.0 Hz, H-9), 7.71 (1H, dd, J = 0.9 and 7.8 Hz, H-10), 8.06 (1H, dd, J = 1.4 and 7.5 Hz, H-7); ¹³C NMR (CDCl₃, 75 MHz): d 19.2 (CH₃), 19.2 (C-4), 21.2 (CH₃), 27.5 (C-3), 77.9 (C-2), 114.2 (C-4a), 124.3 (C-5' orto tolyl), 125.8 (C-6 and C-9), 127.3 (C-6'), 128.9 (C-3' orto tolyl), 130.9 (C-9a), 131.8 (C-5a), 134.6 (C-1'),130.2 (C-6a), 132.4 (C-10a), 135.1 and 138.5 (C-2' and C-4'), 163.5 (C-10b), 178.7 and 179.8 (C-5 and C-10). HRMS (ESI) calcd for C₂₁H₁₈O₃: 318.1256, Found: 318.1892

4-(4-nitrophenyl)-2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11d )

Orange solid, m.p. = 232-235ºC; IR (KBr/cm^-1): 1696, 1645, 1600, 1570, 1513, 1344, 1287, 1233, 1168, 1091, 912, 736, 702. ¹H NMR (300 MHz, CDCl₃): δ 2.19 (1H, dt, J = 2.4 and 14.4 Hz, H-3a syn isomer) and 2.27 (1H, dt, J = 11.2 and 14.4 Hz, H-3a anti isomer), 2.38 and 2.39 (3H, s, CH₃), 2.55 (1H, ddd, J = 5.9, 12.0 and 14.4 Hz, H-3b syn isomer) and 2.61 (1H, ddd, J = 2.2, 7.1 and 14.4 Hz, H-3b anti isomer), 4.31 (1H, dd, J = 7.1 and 11.0 Hz, H-4 anti isomer) and 4.48 (1H, dd, J = 2.4 and 5.9 Hz, H-4 syn isomer), 5.07 (1H, dd, J = 2.4 and 12.0 Hz, H-2 syn isomer) and 5.31 (1H, dd, J = 2.2 and 11.2 Hz, H-2 anti isomer), 7.25 (1H, d, J = 8.1 Hz, H-meta p-tolyl), 7.35 (1H, d, J = 8.1 Hz, H-ortho p-tolyl), 7.38 and 7.47 (1H, d, J = 8.8 Hz, H-ortho 4-nitrophenyl), 7.56-7.94 (1H, m, H-7), 7.56-7.94 (1H, m, H-8), 8.11 (1H, d, J = 8.8 Hz, H-meta 4-nitrophenyl), 8.09-8.23 (1H, m, H-9), 8.09-8.23 (1H, m, H-6). ¹³C NMR (75 MHz, CDCl₃): δ 21.1 (CH₃), 34.9 and 38.4 (C-4), 36.7 and 39.8 (C-3), 80.0 (C-2), 115.9 (C-4a), 123.8 and 123.9 (C-3' 4-nitrophenyl), 124.0 (C-2' 4-nitrophenyl), 125.9 and 126.0 (C-3' p-tolyl), 127.7 (C-8), 128.6 (C-7), 128.8 and 129.0 (C-2' p-tolyl), 129.5 (C-10), 130.3 (C-6a), 130.4 (C-1' p-tolyl), 131.3 (C-9), 131.7 (C-4' p-tolyl), 135.0 (C-10a), 138.9 (C-4' 4-nitrophenyl), 151.1 (C-1' 4-nitrophenyl), 164.9 (C-10b), 177.6 (C-5), 178.7 (C-6). HRMS (ESI) calcd for C₂₆H₁₉NO₅H⁺: 426.1336, Found: 426.4483.

4-Phenyl-2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11e )

Orange solid, m.p. = 92-95 ºC; IR (KBr/cm^-1): 1696, 1653, 1600, 1568, 1382, 1284, 1231, 1164, 1086, 909, 767, 699. ¹H NMR (300 MHz, CDCl₃): δ 2.13-2.37 (1H, m, H-3a, 2.38 and 2.39 (3H, s, CH₃), 2.59 (1H, ddd, J = 2.0, 7.3 and 14.4 Hz, H-3b), 4.20 (1H, dd, J = 7.1 and 11.2 Hz, H-4 anti isomer) and 4.42 (1H, dd, J = 1.7 and 5.4 Hz, H-4 syn isomer), 5.15 (1H, dd, J = 2.7 and 12.0 Hz, H-2 syn isomer) and 5.24 (1H, dd, J = 1.7 and 12.0 Hz, H-2 anti isomer), 7.13-7.38 (4H, m, p-tolyl), 7.13-7.38 (5H, m, Ph), 7.52-7.60 (1H, m, H-7), 7.64-7.70 (1H, m, H-8), 7.88-7.92 (1H, m, H-9), 8.07-8.10 (1H, m, H-6 anti isomer) and 8.12-8.15 (1H, m, H-6 syn isomer). ¹³C NMR (75 MHz, CDCl₃): d 21.1 (CH₃), 34.6 and 38.5 (C-4), 40.6 (C-3), 80.1 (C-2), 117.5 (C-4a), 124.5 (C-3' Ph), 126.0 and 126.1 (C-3' p-tolyl), 126.3 (C-2' Ph), 126.7 and 126.8 (C-4' Ph), 128.4 (C-8), 128.5 and 128.6 (C-7), 129.2 and 129.3 (C-2' p-tolyl), 130.2 (C-6a), 130.8 (C-10), 132.1 (C-1' p-tolyl), 134.8 (C-9), 135.6 (C-4' p-tolyl), 138.6 (C-10a), 143.3 (C-4' Ph), 164.1 (C-10b), 178.0 (C-5), 179.1 (C-6). HRMS (ESI) calcd for C₂₆H₂₀O₃H⁺: 381.1485, Found: 381.4503.

4-(thiophen-2-yl)-2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione ( 11f )

Orange solid, m.p. = 83-87 ºC; IR (KBr/cm^-1): 1696, 1652, 1599, 1568, 1383, 1284, 1231, 1170, 1086, 907, 818, 722, 697. ¹H NMR (300 MHz, CDCl₃): δ 2.28-2.43 (1H, m, H-3a), 2.40 (3H, s, CH₃), 2.68 (1H, ddd, 2.1, 7.1 and 14.4 Hz, H-3b), 4.57 (1H, dd, J = 7.1 and 11.0 Hz) and 4.65 (1H, dd, J = 1.0 and 3.2 Hz) H-4 conformers, 5.23 (1H, dd, J = 1.9 and 11.5 Hz) and 5.35 (1H, dd, J = 4.4 and 10.0 Hz) H-2 conformers, 6.89 and 6.90 (1H, dd, J = 1.0 and 3.4 Hz, H-3' thiophen-2-yl conformers), 6.86 and 6.95 (1H, dd, J = 3.7 and 5.1 Hz, H-4' thiophen-2-y conformers), 7.06 and 7.18 (1H, dd, J = 1.2 and 5.1 Hz, H-5' thiophen-2-yl conformers), 7.24 and 7.25 (1H, d, J = 8.0 Hz, H-meta conformers), 7.30 and 7.36 (1H, d, J = 8.0 Hz, H-ortho conformers), 7.54 and 7.57 (1H, td, J = 1.2 and 7.6 Hz, H-8 conformers), 7.65 and 7.67 (1H, dt, J = 1.2 and 7.6 Hz, H-9 conformers), 7.90 (1H, d, J = 7.6 Hz, H-10), 8.09 and 8.13 (1H, dd, J = 1.5 and 7.6 Hz, H-7 conformers). ¹³C NMR (75 MHz, CDCl₃): δ 21.0 (CH₃), 30.1 and 33.4 (C-4), 37.1 and 40.9 (C-3), 76.6 and 80.0 (C-2), 115.2 and 117.2 (C-4a), 122.7 and 123.9 (C-5' thiophen-2-yl), 124.5 and 124.6 (C-3' p-tolyl), 125.0 (C-8), 126.0 and 126.1 (C-2' p-tolyl), 126.4 and 126.9 (C-10), 128.6 and 128.7 (C-7), 129.3 (C-4' thiophen-2-yl), 130.2 and 130.3 (C-6a), 130.9 and 131.0 (C-9), 131.7 and 131.9 (C-1' p-tolyl), 134.7 and 134.8 (C-3' thiophen-2-yl), 135.3 and 135.7 (C-4' p-tolyl), 138.5 and 138.6 (C-10a), 146.2 and 146.7 (C-2' thiophen-2-yl), 163.0 and 163.4 (C-10b), 177.7 and 178.0 (C-5), 179.0 (C-6). HRMS (ESI) calcd for C₂₄H₁₈O₃SH⁺: 387.1049, Found: 387.4789.

Publication Dates

• Publication in this collection
  30 Oct 2009
• Date of issue
  2009

History

• Accepted
  24 Aug 2009
• Received
  06 Jan 2009